Gene Symbol: kek1
Description: kekkon-1
Alias: BEST:GM02380, CG12283, CT18186, Dmel\CG12283, Dmkek1, GM02380, KEK1, Kek, Kek-1, Kek1, NB1, SD01674, kek, kek-1, kekon, l(2)01433, n(2)k07332, uns, kekkon-1, CG12283-PB, CG12283-PC, Kekkon-1, Kekkon1, Kekon-1, kek1-PB, kek1-PC, kekkon, kekkon 1, kekkonI, unstrung
Species: fruit fly
Products:     kek1

Top Publications

  1. Tanentzapf G, Tepass U. Interactions between the crumbs, lethal giant larvae and bazooka pathways in epithelial polarization. Nat Cell Biol. 2003;5:46-52 pubmed
  2. Ghiglione C, Carraway K, Amundadottir L, Boswell R, Perrimon N, Duffy J. The transmembrane molecule kekkon 1 acts in a feedback loop to negatively regulate the activity of the Drosophila EGF receptor during oogenesis. Cell. 1999;96:847-56 pubmed
    We have identified the Drosophila transmembrane molecule kekkon 1 (kek1) as an inhibitor of the epidermal growth factor receptor (EGFR) and demonstrate that it acts in a negative feedback loop to modulate the activity of the EGFR tyrosine ..
  3. Van Buskirk C, Schupbach T. Versatility in signalling: multiple responses to EGF receptor activation during Drosophila oogenesis. Trends Cell Biol. 1999;9:1-4 pubmed
    ..In posterior follicle cells, EGFR activity is translated into an on-off response, whereas, in dorsal follicle cells, patterning mechanisms are initiated and refined by feedback that modulates receptor activity over time. ..
  4. Musacchio M, Perrimon N. The Drosophila kekkon genes: novel members of both the leucine-rich repeat and immunoglobulin superfamilies expressed in the CNS. Dev Biol. 1996;178:63-76 pubmed
    ..These two molecules, Kek1 and Kek2, show striking conservation in their extracellular domains and have large and more divergent intracellular ..
  5. Brand A, Perrimon N. Raf acts downstream of the EGF receptor to determine dorsoventral polarity during Drosophila oogenesis. Genes Dev. 1994;8:629-39 pubmed
    ..In this assay, human and Drosophila Rafgof are functionally similar, in that either can induce ventral follicle cells to assume a dorsal fate. ..
  6. Pallavi S, Kannan R, Shashidhara L. Negative regulation of Egfr/Ras pathway by Ultrabithorax during haltere development in Drosophila. Dev Biol. 2006;296:340-52 pubmed
    ..These results and other recent findings suggest that homeotic genes may regulate cell fate determination by directly regulating few steps at the top of the hierarchy of selected signal transduction pathways. ..
  7. Mathieu J, Sung H, Pugieux C, Soetaert J, Rorth P. A sensitized PiggyBac-based screen for regulators of border cell migration in Drosophila. Genetics. 2007;176:1579-90 pubmed
    ..We present evidence that an excess of JNK signaling is deleterious for migration in the absence of PVR activity at least in part through Fos transcriptional activity and possibly through antagonistic effects on DIAP1. ..
  8. Matsuoka S, Hiromi Y, Asaoka M. Egfr signaling controls the size of the stem cell precursor pool in the Drosophila ovary. Mech Dev. 2013;130:241-53 pubmed publisher
    ..While excess GSC formation is compensated by the adult stage, insufficient GSC formation can lead to adult ovarioles that completely lack GSCs, suggesting that ensuring an absolute size of the PGC pool is crucial for the GSC system...
  9. Deng W, Ruohola Baker H. Laminin A is required for follicle cell-oocyte signaling that leads to establishment of the anterior-posterior axis in Drosophila. Curr Biol. 2000;10:683-6 pubmed
    ..This is the first evidence that the extracellular matrix is involved in the establishment of a major body axis. ..

More Information


  1. Stephan R, Grevelhörster A, Wenderdel S, Klämbt C, Bogdan S. Abi induces ectopic sensory organ formation by stimulating EGFR signaling. Mech Dev. 2008;125:183-95 pubmed publisher
    ..Concomitantly, we noted changes in tyrosine phosphorylation supporting previous reports that Abi protein stability is linked to tyrosine phosphorylation mediated by Abl. ..
  2. Li Q, Shen L, Xin T, Xiang W, Chen W, Gao Y, et al. Role of Scrib and Dlg in anterior-posterior patterning of the follicular epithelium during Drosophila oogenesis. BMC Dev Biol. 2009;9:60 pubmed publisher
    ..This study may open another window for elucidating role of scrib/dlg in controlling epithelial polarity and cell proliferation during development. ..
  3. Roth S, Jordan P, Karess R. Binuclear Drosophila oocytes: consequences and implications for dorsal-ventral patterning in oogenesis and embryogenesis. Development. 1999;126:927-34 pubmed
    ..Thus, processes exist in the ventral follicular epithelium or in the perivitelline space that compensate for the expansion of dorsal follicle cell fates and consequently allow the formation of a normal embryonic axis. ..
  4. Nagel A, Szawinski J, Fischer P, Maier D, Wech I, Preiss A. Dorso-ventral axis formation of the Drosophila oocyte requires Cyclin G. Hereditas. 2012;149:186-96 pubmed publisher
    ..We propose a role of cycG in processes that regulate translation of Grk and hence, influence EGFR-mediated patterning processes during oogenesis. ..
  5. Queenan A, Ghabrial A, Schupbach T. Ectopic activation of torpedo/Egfr, a Drosophila receptor tyrosine kinase, dorsalizes both the eggshell and the embryo. Development. 1997;124:3871-80 pubmed
    ..The expression of genes known to respond to top/Egfr activation, argos (aos), kekkon1 (kek 1) and rhomboid (rho), was also expanded in the presence of the lambda top construct...
  6. Freeman M. Feedback control of intercellular signalling in development. Nature. 2000;408:313-9 pubmed
    ..These feedback interactions can impart precision, robustness and versatility to intercellular signals. Feedback failure can cause disease. ..
  7. Yan Y, Denef N, Tang C, Schupbach T. Drosophila PI4KIIIalpha is required in follicle cells for oocyte polarization and Hippo signaling. Development. 2011;138:1697-703 pubmed publisher
    ..In PI4KIIIalpha mutant follicle cells, Merlin fails to localize to the apical domain. Our analysis of PI4KIIIalpha mutants provides a new link in Hippo signal transduction from the cell membrane to its core kinase cascade. ..
  8. Speicher S, Garcia Alonso L, Carmena A, Martin Bermudo M, De La Escalera S, Jimenez F. Neurotactin functions in concert with other identified CAMs in growth cone guidance in Drosophila. Neuron. 1998;20:221-33 pubmed
    ..of neurotactin and other genes encoding adhesion/signaling molecules, including neuroglian, derailed, and kekkon1, displayed phenotypic synergy...
  9. Depraetere V. Wingless and naked. Nat Cell Biol. 2000;2:E40 pubmed
  10. Duchek P, Rørth P. Guidance of cell migration by EGF receptor signaling during Drosophila oogenesis. Science. 2001;291:131-3 pubmed
    ..The transforming growth factor-alpha (TGF-alpha)-like ligand Gurken appears to serve as the guidance cue. To mediate this guidance function, EGFR signals via a pathway that is independent of Raf-MAP kinase and receptor-specific. ..
  11. Bai J, Chiu W, Wang J, Tzeng T, Perrimon N, Hsu J. The cell adhesion molecule Echinoid defines a new pathway that antagonizes the Drosophila EGF receptor signaling pathway. Development. 2001;128:591-601 pubmed
    ..Together, our results support a model whereby ED defines an independent pathway that antagonizes EGFR signaling by regulating the activity, but not the level, of the TTK88 transcriptional repressor. ..
  12. Valentine M, Hogan J, Collier S. The Drosophila Chmp1 protein determines wing cell fate through regulation of epidermal growth factor receptor signaling. Dev Dyn. 2014;243:977-87 pubmed publisher
    ..Loss of Chmp1 activity in the Drosophila wing induces a cell fate change from intervein to vein that should provide a useful tool for future studies of ESCRT protein activity. ..
  13. Shravage B, Altmann G, Technau M, Roth S. The role of Dpp and its inhibitors during eggshell patterning in Drosophila. Development. 2007;134:2261-71 pubmed
  14. Fan Y, Bergmann A. Distinct mechanisms of apoptosis-induced compensatory proliferation in proliferating and differentiating tissues in the Drosophila eye. Dev Cell. 2008;14:399-410 pubmed publisher
    ..In summary, dependent on the developmental potential of the affected tissue, different caspases trigger distinct forms of compensatory proliferation in an apparent nonapoptotic function. ..
  15. Perrimon N, McMahon A. Negative feedback mechanisms and their roles during pattern formation. Cell. 1999;97:13-6 pubmed
  16. Hall L, Alexander S, Chang M, Woodling N, Yedvobnick B. An EP overexpression screen for genetic modifiers of Notch pathway function in Drosophila melanogaster. Genet Res. 2004;83:71-82 pubmed
    ..Our results suggest that a genetic screen that combines partial loss of function with random gene overexpression might be a useful strategy in the analysis of developmental pathways. ..
  17. Ferguson S, Blundon M, Klovstad M, Schupbach T. Modulation of gurken translation by insulin and TOR signaling in Drosophila. J Cell Sci. 2012;125:1407-19 pubmed publisher
    ..This model might explain how flies can maintain the translation of developmentally important transcripts during periods of nutrient limitation when bulk cap-dependent translation is repressed. ..
  18. Leevers S. What goes up must come down. Nat Cell Biol. 1999;1:E10-1 pubmed
  19. Peretz G, Bakhrat A, Abdu U. Expression of the Drosophila melanogaster GADD45 homolog (CG11086) affects egg asymmetric development that is mediated by the c-Jun N-terminal kinase pathway. Genetics. 2007;177:1691-702 pubmed
    ..We found that eggshell polarity defects caused by D-GADD45 overexpression were dominantly suppressed by mutations in the JNK pathway, suggesting that the JNK pathway has a novel, D-GADD45-mediated, function in the Drosophila germline. ..
  20. Bernardi F, Duchi S, Cavaliere V, Donati A, Andrenacci D, Gargiulo G. Egfr signaling modulates VM32E gene expression during Drosophila oogenesis. Dev Genes Evol. 2007;217:529-40 pubmed
    ..This may suggest that a fine tuning of the expression of specific eggshell structural genes could be part of the complex process that leads to a proper eggshell assembly. ..
  21. Steinhauer J, Liu H, Miller E, Treisman J. Trafficking of the EGFR ligand Spitz regulates its signaling activity in polarized tissues. J Cell Sci. 2013;126:4469-78 pubmed publisher
    ..Taken together, our data support the model that localized trafficking of the pro-protein restricts its ability to activate the receptor in polarized tissues. ..
  22. Li Z, Liu S, Cai Y. EGFR/MAPK signaling regulates the proliferation of Drosophila renal and nephric stem cells. J Genet Genomics. 2015;42:9-20 pubmed publisher
    ..Together, our data suggest a principal role of EGFR/MAPK signaling in regulating RNSC proliferation, which may provide important clues for understanding mammalian kidney repair and regeneration following injury. ..
  23. Sapir A, Schweitzer R, Shilo B. Sequential activation of the EGF receptor pathway during Drosophila oogenesis establishes the dorsoventral axis. Development. 1998;125:191-200 pubmed
    ..One class of genes (e.g. kekon) is induced by the DER pathway at all stages...
  24. Derheimer F, MacLaren C, Weasner B, Alvarado D, Duffy J. Conservation of an inhibitor of the epidermal growth factor receptor, Kekkon1, in dipterans. Genetics. 2004;166:213-24 pubmed
    ..b>Kekkon1 (Kek1) represents one such inhibitor...
  25. Ghiglione C, Amundadottir L, Andresdottir M, Bilder D, Diamonti J, Noselli S, et al. Mechanism of inhibition of the Drosophila and mammalian EGF receptors by the transmembrane protein Kekkon 1. Development. 2003;130:4483-93 pubmed
    The transmembrane protein Kekkon 1 (Kek1) has previously been shown to act in a negative feedback loop to downregulate the Drosophila Epidermal Growth Factor Receptor (DER) during oogenesis...
  26. Ghiglione C, Bach E, Paraiso Y, Carraway K, Noselli S, Perrimon N. Mechanism of activation of the Drosophila EGF Receptor by the TGFalpha ligand Gurken during oogenesis. Development. 2002;129:175-86 pubmed
    ..These two proteins collaborate to promote an activating proteolytic cleavage and release of Grk. After cleavage, the extracellular domain of Grk is secreted from the oocyte to activate the Egfr in the follicular epithelium. ..
  27. Goode S, Melnick M, Chou T, Perrimon N. The neurogenic genes egghead and brainiac define a novel signaling pathway essential for epithelial morphogenesis during Drosophila oogenesis. Development. 1996;122:3863-79 pubmed
  28. Wessells R, Grumbling G, Donaldson T, Wang S, Simcox A. Tissue-specific regulation of vein/EGF receptor signaling in Drosophila. Dev Biol. 1999;216:243-59 pubmed
    ..Finally, we show that other factors modulate the potential of Vn so that induction of Vn/DER target genes in the wing pouch is cell specific. ..
  29. Peri F, Roth S. Combined activities of Gurken and decapentaplegic specify dorsal chorion structures of the Drosophila egg. Development. 2000;127:841-50 pubmed
    ..This intersection also induces rhomboid expression and thereby initiates the positive feedback loop of EGF receptor activation, which positions the dorsal appendages along the dorsal-ventral egg axis. ..
  30. Alvarado D, Rice A, Duffy J. Knockouts of Kekkon1 define sequence elements essential for Drosophila epidermal growth factor receptor inhibition. Genetics. 2004;166:201-11 pubmed
    ..One inhibitor, the transmembrane protein Kekkon1 (Kek1) functions during oogenesis in a negative feedback loop to directly attenuate EGFR activity...
  31. Upadhyai P, Campbell G. Brinker possesses multiple mechanisms for repression because its primary co-repressor, Groucho, may be unavailable in some cell types. Development. 2013;140:4256-65 pubmed publisher
    ..Gro insufficiency during oogenesis can be explained by its downregulation in Brk-expressing cells through phosphorylation downstream of EGFR signaling. ..
  32. MacLaren C, Evans T, Alvarado D, Duffy J. Comparative analysis of the Kekkon molecules, related members of the LIG superfamily. Dev Genes Evol. 2004;214:360-6 pubmed
    ..One LIG whose function has been investigated is the Drosophila protein Kekkon1 (Kek1)...
  33. Bogdan S, Klämbt C. Epidermal growth factor receptor signaling. Curr Biol. 2001;11:R292-5 pubmed
  34. Layalle S, Ragone G, Giangrande A, Ghysen A, Dambly Chaudiere C. Control of bract formation in Drosophila: poxn, kek1, and the EGF-R pathway. Genesis. 2004;39:246-55 pubmed
    ..We have identified the gene kek1, described as an inhibitor of the EGF-R signaling pathway, in a screen for poxn downstream genes...
  35. Zinn K, Sun Q. Slit branches out: a secreted protein mediates both attractive and repulsive axon guidance. Cell. 1999;97:1-4 pubmed
  36. Kitadate Y, Kobayashi S. Notch and Egfr signaling act antagonistically to regulate germ-line stem cell niche formation in Drosophila male embryonic gonads. Proc Natl Acad Sci U S A. 2010;107:14241-6 pubmed publisher
    ..Thus, we propose that SGPs sense PGC number via signals from PGCs to SGPs that modulate niche size, and that this serves as a mechanism for securing GSCs...
  37. Zartman J, Kanodia J, Cheung L, Shvartsman S. Feedback control of the EGFR signaling gradient: superposition of domain-splitting events in Drosophila oogenesis. Development. 2009;136:2903-11 pubmed publisher
    ..Two negative-feedback loops provided by the intracellular inhibitors of EGFR signaling, Kekkon-1 and Sprouty, control the number and position of Broad-expressing cells and in this way influence eggshell ..
  38. Xia F, Li J, Hickey G, Tsurumi A, Larson K, Guo D, et al. Raf activation is regulated by tyrosine 510 phosphorylation in Drosophila. PLoS Biol. 2008;6:e128 pubmed publisher
    ..Since Y510 is a conserved residue in the kinase domain of all Raf proteins, this mechanism is likely evolutionarily conserved. ..
  39. Alvarado D, Rice A, Duffy J. Bipartite inhibition of Drosophila epidermal growth factor receptor by the extracellular and transmembrane domains of Kekkon1. Genetics. 2004;167:187-202 pubmed
    ..better understand the regulation of EGFR activity we investigated inhibition of EGFR by the transmembrane protein Kekkon1 (Kek1)...
  40. Motola S, Neuman Silberberg F. spoonbill, a new Drosophila female-sterile mutation, interferes with chromosome organization and dorsal-ventral patterning of the egg. Dev Dyn. 2004;230:535-45 pubmed
    ..This finding places the spoonbill gene upstream of both pathways. ..
  41. Brendza R, Serbus L, Saxton W, Duffy J. Posterior localization of dynein and dorsal-ventral axis formation depend on kinesin in Drosophila oocytes. Curr Biol. 2002;12:1541-5 pubmed
    ..Alternatively, kinesin I may facilitate cytoplasmic dynein-based anterodorsal forces by repositioning dynein toward microtubule plus ends. ..
  42. Guichet A, Peri F, Roth S. Stable anterior anchoring of the oocyte nucleus is required to establish dorsoventral polarity of the Drosophila egg. Dev Biol. 2001;237:93-106 pubmed
    ..cap 'n' collar mutants, therefore, allow for the study of the influence of Grk signal duration on DV patterning in the follicular epithelium. ..
  43. Goentoro L, Yakoby N, Goodhouse J, Schupbach T, Shvartsman S. Quantitative analysis of the GAL4/UAS system in Drosophila oogenesis. Genesis. 2006;44:66-74 pubmed
    ..The imaging-based strategy described here can be used to quantify other GAL4 drivers in Drosophila and other organisms. ..
  44. Firth L, Baker N. EGF receptor signaling: a prickly proposition. Curr Biol. 2003;13:R773-4 pubmed
  45. Chen Y, Pedersen J, Wandall H, Levery S, Pizette S, Clausen H, et al. Glycosphingolipids with extended sugar chain have specialized functions in development and behavior of Drosophila. Dev Biol. 2007;306:736-49 pubmed
    ..Despite the similar enzymatic activity, we provide evidence that the two enzymes are not functionally redundant in vivo, but direct distinct developmental functions of GSL. ..
  46. Atkey M, Lachance J, Walczak M, Rebello T, Nilson L. Capicua regulates follicle cell fate in the Drosophila ovary through repression of mirror. Development. 2006;133:2115-23 pubmed
    ..We propose that Capicua regulates the pattern of follicle cell fates along the dorsoventral axis by blocking the induction of appendage determinants, such as mirror, by anterior positional cues. ..
  47. Stevaux O, Dimova D, Ji J, Moon N, Frolov M, Dyson N. Retinoblastoma family 2 is required in vivo for the tissue-specific repression of dE2F2 target genes. Cell Cycle. 2005;4:1272-80 pubmed
    ..These results demonstrate that RBF2 has a unique function in repressing E2F-regulated differentiation markers and that dE2F2 and RBF2 are required to regulate different sets of target genes in different tissues. ..